The present invention relates generally to biological sample analyzers used to perform assays of patient specimen samples. More particularly, the present invention relates to a method and system for the scheduling an adaptive rinse operation as part of the operating steps for performing assays of biological samples in an automatic analyzer.
Biological sample analyzers, of the type considered herein, are automated instruments that may be used in hospitals, clinics, laboratories, or other locations, to run routine tests (assays) on samples of patient specimens such as blood, spinal fluid, urine, serum, plasma, and so on. An automated analyzer of the type discussed herein includes an analyzer unit that runs tests on a number of patient specimen samples that are loaded into the unit. An operator-user prepares the samples by placing portions of the patients' specimen samples into a number of like-sized sample containers. These samples may be diluted or otherwise treated, depending upon the type of analyzer used, the type of assay being performed, and other factors. The containers are then placed in the analyzer unit. The containers may first be placed in a rack or carousel that is then placed in the analyzing unit. The rack may accommodate a number of sample containers, e.g. 24. In addition, one or more appropriate chemical reagents, needed to perform the assays, are also placed in the analyzer unit. In order to mix reagents with the samples, the analyzer unit may also include a fluid moving system, such as a robotic probe mounted on a boom, which is adapted to draw up portions of the reagents and/or samples and expel them into appropriate locations, e.g. additional cells such as reaction cells provided in the sample containers, where a reaction can take place. The analyzer unit also may include a means for detecting a reaction in the reaction cells. This may include an optical detector to observe fluorescence reactions and make optical measurements to obtain a result for each sample. The analyzer unit may also typically include other mechanical systems to move the sample containers and the probe. The analyzer unit may also provide for cleaning the probe between certain tasks in order to avoid contamination between samples. For this purpose, the analyzer unit may also include a washing station and a waste dispensing container to hold the used rinse solution. (For purposes of this specification and claims, the terms "rinse" and "cleaning solution" are used interchangeably).
After the operator-user loads the specimen samples, enters appropriate instructions, and starts the unit, the analyzer runs unattended. When placed in operation, the analyzer unit, using the appropriate chemical reagent, runs the same test on each of the samples in the sample containers and will perform identical operations on each of the samples loaded in the rack. When it is finished, the analyzer prints out or otherwise reports on the results of its testing.
Biological analyzers utilize different chemistries for performing assays of specimen samples. One type of assays used in biological analyzers includes immunoassays and solid phase procedures. Analyzers for performing immunoassays in general and enzyme immunoassays in particular are known in the art.
A biological analyzer that utilizes immunoassay chemistry to perform assays of specimen samples loaded therein is the IMx.RTM. analyzer introduced in 1988 by Abbott Laboratories, of North Chicago, Ill. (A description of the IMx analyzer is included in "The Abbott IMx Automated Benchtop Immunochemistry Analyzer System", by Fiore, M. et al., Clinical Chemistry, Vol. 34, No. 9, 1988, which is specifically incorporated herein by reference in its entirety). The IMx analyzer is a biological sample analyzer that has been developed for use in conjunction with solid phase immunoassay procedures to perform a variety of assays (such as sandwich and competitive assays). The IMx analyzer uses a technology referred to as microparticle capture enzyme immunoassay (MEIA) and fluorescence polarization immunoassay (FPIA). The IMx analyzer includes a microprocessor used to control a robotic arm with 2 degrees of freedom and a rotating carousel to process the samples for assay. One assay can be done on each of 24 specimen samples in 30-40 minutes or more unattended after loading (i.e. with "walk away" automation). Assay results are output to a printer or a computer interface.
A biological sample analyzer, such as the IMx analyzer described above, can execute the steps required for performing assays of up to 24 specimen samples, including the steps of counting the samples, identifying which assay to run, warming the reagents and reaction cells to appropriate temperatures, pipetting the reagents and samples, diluting samples if required, timing critical assay steps such as incubations, washing unbound conjugate, quantifying the fluorescence signal and performing data reduction to yield a useful result.
The container used for holding each of the specimen samples for a biological sample analyzer, such as the IMx analyzer, may be a disposable assay cartridge having a plurality of wells, with at least one reaction well and one separation well. The separation well may contain a fibrous matrix positioned across its entrance and an absorbent material positioned below the fibrous matrix. Microparticles react with an analyte containing sample and one or more reagents to form a complex. This complex is immobilized on the matrix of the separation cell. The excess sample and reagent are washed through the matrix and captured in the absorbent material below.
The results of the reactions may be read using known optical detection techniques. For example, using conventional solid phase procedures, an analyte can be labeled or tagged with an enzyme which in the presence of its substrate fluoresces and emits light at a known wave length. The rate at which the fluorescent product is produced is indicative of the concentration of the analyte in the biological sample. A conventional fluorometer is suitable for illuminating the fibrous matrix with a beam of light having the appropriate excitation wave length. The fluorometer also detects the intensity of the light at the emission wave length assays. Using this type of solid phase technology has been found to provide a high degree of sensitivity.
A biological sample analyzer, such as the IMx analyzer, provides for performing assays of patients' specimen samples and reading the results of such assays in a mass production type manner. This allows such assays to be made available quickly and conveniently.
The steps that the instrument systems follow to perform the assay in the biological analyzer are included in a program called a protocol. The protocol is written by an assay developer and may be included on the module. The protocol is a series of steps or instructions for the instrument systems to perform including time constraints on when the steps are to be performed. These steps could include mixing the sample with one or more reagents in a mixing cell, providing an incubation time, and measuring a reaction. Often, certain steps for each sample have to be separated by an incubation time to allow for a reaction to take place. Instrument systems, such as the probe, may perform some of the steps for one specimen sample until an incubation time is needed and then the probe performs a similar series of operations on another of the specimens, and so forth. When moving from one sample to the next, the probe may have to be decontaminated to prevent carryover by inserting it into a rinse solution. Commands to perform a rinse operation are included in the protocol. With this type of operation, the assay developer would typically write an instruction in the assay protocol to clean the probe after a series of operations to prevent contaminating the next sample. Because the types of samples and reagents is known to the assay developer, the assay developer could instruct the analyzer to perform a cleaning operation appropriate to clean the probe to prevent carry over. Different cleaning operations are necessary depending upon the type of specimens and reagents being handled. For example, it might be determined that the probe would be sufficiently cleaned by drawing into it a certain number of ml of the rinse solution and expelling the rinse. For other specimens and reagents, it may be necessary to perform the cleaning operation twice. Alternatively, it may be necessary to draw the rinse into the probe and hold it for a certain number of seconds. In a biological analyzer, such as the IMx analyzer, dozens of different types of rinses may be used depending upon the needs of assay.
Even though such analyzers can provide significant advantages by performing assays quickly and conveniently, further advantages for the user could be obtained if the overall through put of the analyzer could be increased. One way to provide even more advantages and convenience for users of biological analyzers would be to provide the capability to perform more than one assay on the specimen samples in an unattended run. Although a biological analyzer such as the IMx analyzer can perform different types of assays and can perform assays on a number of specimen samples unattended, the analyzer can run only one type of assay at a time. If a different type of assay is to be performed, the analyzer would have to be reloaded with different reagents. Also, because different types of assays may require different amounts of the sample specimen, different amounts of reagents, different processing steps, different incubation times, etc., the analyzer would also be reset at the beginning of the run to perform the new assay. In the case of the IMx analyzer, a different memory module may have to be inserted containing the instructions for the analyzer unit for performing the different assay. Thus, even if only a few of several different types of assays need to be run, the operator-user has to load and run the analyzer for the first type of assay for only a few samples and then reload the analyzer to run the second type of assay on another batch of samples using perhaps different reagents. It is recognized that for many users of the IMx analyzer, or other biological sample analyzers, it would be convenient and advantageous to be able to perform more than one type of assay during an unattended run.
Although analyzers having the capability to perform more than one assay in an unattended run have the potential to provide further advantages and convenience for the operator-user, when the operator-user is given the capability to choose which type of assays to perform in an unattended run, providing this feature presents several obstacles relating to the analyzer operation. One obstacle associated with operating an analyzer to perform more than one assay in a run relates to carryover. In the prior analyzers that perform only one assay in an unattended run, the developer could readily determine the sequence of operating steps and provide the appropriate instruction in the protocol for the type of cleaning operation, such as rinse, needed to prevent carryover. However, in an analyzer in which more than one assay is being performed, there is a large number of possible permutations of load list combinations available. For example, if there are 24 specimen samples in the carousel rack and the operator-user is permitted to select any one of three different assays to be performed on the samples, there are almost 2500 different permutations of possible combinations of assays and samples that the user can select. If the operator-user is permitted to select any one of four different assays to be performed on the 24 samples, there are approximately 10,000 different permutations of possible combinations. Thus, the assay developer is no longer able to know with certainty which samples will be handled by sequential operations of the analyzer instrument systems, such as the probe or which reagents will be used for subsequent operations or even which operations will be performed sequentially. For example, the potential exists for an analyte to be present in a sample upon which an assay not specific to that analyte is performed to be carried over to a sample upon which an assay specific to that analyte is being performed thereby causing a false positive. Whereas in single assay runs, the assay developer could predict with a certainty the type of rinse needed to avoid contamination, with the load list combinations present with more-than-one assay runs, the number of permutations of possible operating sequences is high enough that it becomes difficult to predict the type of rinse operation is required.
One way to address this concern is to establish a rinsing safety factor high enough to always effectively clean the probe regardless of the sequence of operations. Thus, the assay developer would use a strong rinse or a large quantity or duration of rinse between all operating steps. This rinse would be based upon the worst case contamination concern. If the worst case contamination were always provided for, the analyzer would use a considerable amount of rinse and would likely be using more rinse than is needed between instrument system operations for many load list permutations.
Using more rinse than is necessary is inconvenient and requires the refilling the cleaning solution container frequently. Using more rinse than is necessary requires disposing of the large quantity of rinse waste generated. Moreover, excess rinse can lead to problems. For example, if too much of a certain rinse is used and some of it carries over to another sample for another assay that is sensitive to that rinse, it may interfere with the chemical reactions in performing the assay for the latter sample.
Another problem related to operating an analyzer to perform more than one assay in a run relates to warming the probe. As mentioned above, assays and particularly immunoassays are sensitive to the temperature. For that reason, provision is made to stabilize the temperature as much as possible. When operating an analyzer with more than one assay type and the high number of possible combinations of operations, it is possible that the probe may be idled for a period of time and possibly cool off. one way to ensure that this does not happen is by inserting the probe into the rinse which is maintained at a preferred temperature. This operation is referred to as "pre-warming". In an analyzer that performs more than one assay and that has a high number of possible combinations of operating steps, it cannot readily be determined when such a pre-warming step should be performed if at all.
Accordingly, it is an object of the present invention to provide a biological sample analyzer, and a method and system for operation thereof, that provides for a cleaning operation to prevent carryover and a pre-warming operation when needed, especially when more than one type of assay is performed on patient specimen samples loaded therein.
It is a further object of the present invention to provide for a variable cleaning operation sufficient to prevent contamination of the fluid handling systems and which reduces excessive waste and improves through put.